Controlled Recrystallization of Tubular Vinpocetine Crystals with Increased Aqueous Dissolution Rate and In Vivo Bioavailability

Vinpocetine was a BCS II drug, whose clinical applications had suffered from low oral bioavailability because of its inefficient dissolution in the GI tract. As the dissolution rate depended on the surface area of the drug crystals, we herein explored shape-controlled recrystallization via antisolvent process as an excipient-free strategy to improve the bioavailability of VIN. By adjusting the water/ethanol ratio, initial VIN concentration, and temperatures, morphologies of the crystalline products could be finely tuned from three-dimensional cubes and tubes, to two-dimensional frizzled plates, and finally to zero-dimensional microparticle clusters. Morphology analysis and in situ FBRM surveillance of the growing process suggested that a diffusion-limited crystal growth mechanism was responsible for the shape variation of VIN products. Finally, we tested the in vitro dissolution efficiency as well as the in vivo bioavailability of recrystallized VIN crystals. Results manifested that the tubular crystal showed a faster dissolution behavior as compared with the raw VIN, achieving an increased AUC_0‑t of 484.0 ± 24.6 ng/mL·h, which was 1.3-fold that of the raw VIN product (386.6 ± 22.8 ng/mL·h). To the best of our knowledge, this was one in vitro to in vivo report for bioavailability improvement of BCS II drug by applying the shape-controlled recrystallization strategy.